Potential contribution of mitochondrial (mt) DNA Damage Associated Molecular Patterns (DAMPs) in transfusion products to the development of Acute Respiratory Distress Syndrome (ARDS) after multiple transfusions.

Introduction: Massive transfusions are accompanied by an increased incidence of a particularly aggressive and lethal form of acute lung injury (delayed TRALI) which occurs >24 hours after transfusions. In light of recent reports showing that mtDNA DAMPs are potent pro-inflammatory mediators, and that their abundance in the sera of severely injured or septic patients is predictive of clinical outcomes, we explored the idea that mtDNA DAMPs are present in transfusion products and are associated with the occurrence of delayed TRALI. Methods: We prospectively enrolled fourteen consecutive severely injured patients that received greater than three units of blood transfusion products and determined if the total amount of mtDNA DAMPs delivered during transfusion correlated with serum mtDNA DAMPs measured after the last transfusion, and whether the quantity of mtDNA DAMPs in the serum predicted development of ARDS. Results: We found detectable levels of mtDNA DAMPs in PRBCs (3+/-0.4 ng/mL), FFP (213.7+/- 65 ng/mL), and platelets (94.8+/-69.2), with the latter two transfusion products containing significant amounts of mtDNA fragments. There was a linear relationship between the mtDNA DAMPs given during transfusion and the serum concentration of mtDNA fragments (R2=0.0.74, p

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